Radiation exposure can occur from medical imaging and therapy, natural background radiation from cosmic rays or radon, and intentional exposure through radiation bioterrorism. This Independent Scientist Award will give me the opportunity to focus on research to dissect mechanisms of radiation response and injury by utilizing genetically engineered mice. Ultimately, this information will lay the groundwork for improved cancer therapy, space exploration, and novel countermeasures against radiation. This Independent Scientist (K02) award will support Dr. Kirsch to use mouse genetics to study mechanisms of acute and late effects from radiation therapy. These in vivo studies will provide a mechanistic foundation for the design of safe and effective countermeasures against radiation that do not inadvertently increase late effects of radiation.